Advances in Outpatient Diabetes Care: Algorithms for Care and the Role of Injectable Therapies

Module D

1

Learning Objectives

• Apply the principles of the comprehensive diabetes algorithms to patients with type 2 diabetes

• Design therapeutic options to dual therapy in patients not well-controlled by metformin alone that are associated with a low risk of hypoglycemia and weight gain

• Identify therapeutic options for prandial control in basal insulin–treated patients other than prandial insulin when intensification of therapy is required

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Case Study: Philip

3

• 65-year-old African-American man

• Retired executive, lives with wife

• Hospital admission for motor vehicle accident medical history

– No prior history of DM

– Polyuria, fatigue

• BMI = 30 kg/m2 (overweight)

• Only modestly active

• Family history: brother treated for T2DM

• Hypertension

– Lisinopril 20 mg daily

BMI = body mass index; DM = diabetes mellitus; T2DM = type 2 diabetes mellitus.

Admission Orders

• Consider obtaining an A1C level in patients with

– Diabetes admitted to the hospital if the result of testing in the previous 2–3 months is not immediately available

– Risk factors for undiagnosed diabetes who exhibit hyperglycemia in the hospital

4

A1C = glycated hemoglobin. Umpierrez GE et al; Endocrine Society. J Clin Endocrinol Metab. 2012;97(1):16–38. American Diabetes Association. Diabetes Care. 2014;37(suppl 1):S14–80.

A1C ≥ 6.5%

Start POC BG monitoring x 24-48h

Check A1C level

Initiate POC BG monitoring according to

clinical status

Glucose management and monitoring

No history of diabetes BG <140 mg/dL

No history of diabetes but BG >140 mg/dL

History of diabetes

Diagnosis and Recognition of Hyperglycemia and Diabetes in the Hospital Setting

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POC BG = point-of-care blood glucose testing.

Adapted from Umpierrez GE et al; Endocrine Society. J Clin Endocrinol Metab. 2012;97(1):16–38.

Admission Assess all patients for a history of diabetes Obtain laboratory BG testing on admission

Hyperglycemia in the Hospital and Status Post-Discharge

19.50

9.6

28

0.00

5.00

10.00

15.00

20.00

25.00

30.00

Established diabetes Newly diagnosed diabetes Returned to normoglycemia,but had stress hyperglycemia

6

Sample of a managed care outpatient database (8547 patients) with linkage to inpatient data from June 1, 2003, to June 30, 2006.

Nearly 60% of patients either had DM or manifested hyperglycemia (defined here as BG >130 mg/dL).

Waddell M et al. Postgrad Med. 2009;121(3):61–66.

Perc

ent

Philip Workup and Diagnosis

• Admission A1C = 9.1%

• FPG = 195 mg/dL

• Normal sensory exam

• BP = 135/80 mm Hg

• BMI = 30 kg/m2

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• Diagnosis: newly diagnosed uncontrolled T2DM

• Philip is treated with basal-bolus insulin in the hospital to a BG <140 mg/dL

BP = blood pressure; FPG = fasting plasma glucose.

Discharge Considerations

• What are your discharge plans for this patient?

• Will he be discharged on insulin therapy?

• When and where will follow-up take place?

• What education does he need prior to discharge?

Guideline Approach to Therapy in Patients With Newly Diagnosed Type 2 Diabetes—Applying It to Philip

Lifestyle intervention ±

metformin

Will we implement with

this patient?

Yes or No

Lifestyle intervention is cornerstone therapy for all patients and most patients will receive metformin unless they have

contraindications or can’t tolerate it

Depending on his A1C level, consider

combination therapy or insulin

eg, If A1C ≥7.5%: consider combination

therapy. If A1C ≥9: consider insulin

Let’s come back and talk about where Philip is

If A1C level not at target (3–6

months), we’ll add more therapy

This will depend on his BMI

For example, if his BMI <30, DPP-4 inhibitor

(consider GLP-1 RA, SGLT-2 inhibitor); if it is 35> BMI >30, GLP-1 RA, SGLT-2 inhibitors

DPP-4 inhibitor and if BMI >35, GLP-1 RA, SGLT-2 inhibitors

Consider bariatric surgery in nonresponders

9

Raz I. Diabetes Care. 2013;36(suppl 2):S139–S144.

Setting Glycemic Goals for Philip

• Age – 64 years

• BMI – 28.6 kg/m2 (overweight)

• A1C level – Elevated on admission at 9.1%

• Lifestyle – Only moderately active

• Cardiovascular – Well-controlled hypertension (135/80 mm Hg)

– History of myocardial infarction

– Lipid profile not optimal (LDL <70 mg/dL but HDL not at goal)

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What glycemic goal would you set for Philip? What other treatment goals should he have?

Reducing the Risk of T2DM Complications: Comprehensive Diabetes Management

11

American Diabetes Association. Diabetes Care. 2014;37(suppl 1):S14–S80.

Setting Individualized Glycemic Goals in T2DM 2012 ADA/EASD Position Statement

12

ADA = American Diabetes Association; EASD = European Association for the Study of Diabetes. Inzucchi S et al. Diabetes Care. 2012;35(6):1364–1379. Ismail-Beigi F et al. Ann Intern Med. 2011;154(8):554–559.

Philip

• Target A1C level: 7.0%

• Physician begins discussing pharmacotherapy for Philip

• Diabetes educator consult

– Patient education

– Detailed dietary and exercise recommendations

– Weight-loss strategies

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Weight Reduction in T2DM

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• Calorie restriction

– Key factor for weight loss

– Moderate calorie restriction recommended

– 500–1000 kcal/day fewer than baseline intake

• Dietary changes

– Reduce saturated and trans fatty acids, cholesterol, and sodium

• Behavioral modification

– Self-monitoring of food intake with daily log

– Stimulus control

– Cognitive restructuring

– Stress management

• Physical activity

– At least 150 minutes/week of moderate activity

– Aerobic, resistance, flexibility training

In patients with T2DM, weight loss and exercise can reduce insulin resistance and hepatic glucose production.

Bantle JP et al. Diabetes Care. 2008;31(suppl 1):S61–S78; Brown A et al. Postgrad Med. 2010;122(1):163–171; Inzucchi SE et al. Diabetologia. 2012;55(6):1577–1596; Ismail-Beigi F. N Engl J Med. 2012;366(14):1319–1327; National Institutes of Health. Obes Res. 1998;6(suppl 2):51S–209S.

LOOK AHEAD Study Intensive Lifestyle Intervention and Risk Reduction

• Primary objective

– To examine, in overweight volunteers with T2DM, the long-term effects of an intensive lifestyle intervention program designed to achieve and maintain weight loss by decreased caloric intake and increased physical activity

• Comparison

– Control condition involving a program of diabetes support and education

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Look AHEAD Research Group. Arch Intern Med. 2010;170(17):1566–1575.

LOOK AHEAD Study Intensive Lifestyle Intervention and Risk Reduction

• Diet modification, exercise, behavioral training

• Group support with in-person and telephone follow-ups

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Parameter Lifestyle Intervention (n = 2570)

Support and Education (n = 2575)

Weight loss, % –6.5 –0.88a

Treadmill fitness, % METS 12.74 1.96a

A1C level –0.36 –0.09a

Systolic BP, mm Hg –5.33 –2.97a

Diastolic BP, mm Hg –2.92 –2.48b

HDL-C, mg/dL 3.67 1.97a

Triglycerides, mg/dL –25.56 –19.75b

aP <0.001; bP = 0.01. HDL-C = high-density lipoprotein cholesterol; MET = metabolic equivalent.

Look AHEAD Research Group. Arch Intern Med. 2010;170(17):1566–1575.

Effect of Antihyperglycemic Drugs on A1C Level, Hypoglycemia, Weight (Injectable Therapies Are Highlighted)

Drug A1C Reduction (%) Hypoglycemia Incidence (%)a

Weight Effects (kg)

Sulfonylureas 1–2 18–30 +2

Pioglitazone 0.5–1.4 0–3.7a +0.9 to +2.6

Linagliptin 0.4 0.3a No change

Saxagliptin 0.4–0.5 3–5a –0.1 to –1.2

Sitagliptin 0.6–0.8 <3-5a –0.2 to –0.8

Exenatide twice daily 0.5–1 4–5 –2.8 to –3.1

Liraglutide 0.84–1.14 8–12 –1 to –2.26

Exenatide once weekly 1.5 5-2 –2

SGLT-2 inhibitors 0.5–0.7 1.4 –1.1 to –2.2

Basal insulinb 1.5–3.5c 29.9–61.2 +2 to +4

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aSimilar to placebo. bIncludes NPH, insulin glargine, and insulin detemir. cNo dose or A1C-lowering limit. Exenatide once weekly not approved for use with basal insulin.

Adapted from Boland CL et al. Ann Pharmacother. 2013;47(4):490–505; and Monami M et al. Diabetes Obes Metab. 2014;16(5):457–466.

Philip Discharge Planning

– Discuss with the patient the need for basal insulin in addition to oral agents

– Educator to provide hands-on instruction on administration techniques

– Provide education to caregiver/family if possible – Comprehensive outpatient education should be scheduled

• Philip is discharged on oral metformin 1000 mg bid and a basal insulin pen device, 0.2 u/kg in the evening with instructions to self-titrate to an FPG level of 70–130 mg/dL – Some might suggest lower boundary of 80 mg/dL as in

3–0–3 algorithm, given that Philip is new to insulin and has a prior history of myocardial infarction

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Predischarge Checklist

• Diet information

• Monitor/strips & Rx

• Rx for/supplies of medications, insulin, needles

• Treatment goals

• Contact phone numbers

• “Medi-Alert” bracelet

• “Survival Skills” training – Meal planning

– Sick day planning

– Involve nursing, dietitian, diabetes educator

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“Survival Skills” to Be Taught Before Discharge

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• Basic understanding of what diabetes is

• How and when to take diabetes medications

• Basic knowledge of effect of carbohydrates on glucose levels

• Recognition, treatment, and prevention of hypoglycemia

• Self-monitoring of BG and implication of results

• What to do during illness

• How to dispose of lancets and insulin syringes

Moghissi ES et al; American Association of Clinical Endocrinologists; American Diabetes Association. Endocr Pract. 2009;15(4):353–369.

Transition to Discharge

• Does patient have a glucose monitor for home use?

• Is patient clear about the diabetes therapy after discharge?

• Does patient have appropriate outpatient follow-up appointment with primary care, specialist, diabetes specialist clinic?

• Additional attention to difficulties with insurance, transportation, etc

• Divide material up throughout course of hospital stay; support and reinforce with written material; ensure that follow-up connection is made with outpatient provider

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Specific Advantages of Main Drug Classes

• Metformin – First-line therapy in most consensus algorithms

• Large safety margin • Can be used by most patients • Decreases hepatic glucose production, has a mild effect on

peripheral resistance, and increases both total and active endogenous GLP-1 in response to food

• Might also be cardioprotective in obese T2DM patients • Reduction in mortality in UKPDS • Lowers risk of cancer in T2DM patients

• Insulin – Most powerful agent to lower glucose; no dose limit to

efficacy; indicated when A1C levels above 9%

22

Garber AJ et al. Endocr Pract. 2013;19(3):536–557. Inzucchi SE et al. Diabetes Care. 2012;35(6):1364–1379. Raz I. Diabetes Care. 2013;36(suppl 2):S139–S144.

Guideline Approach to Therapy in Patients With Newly Diagnosed Type 2 Diabetes – Philip

23

Raz I. Diabetes Care. 2013;36(suppl 2):S139–S144.

Set A1C goal 7%

Lifestyle intervention ±

metformin

Diet, exercise program set up

Metformin 1 g bid prescribed

If A1C ≥7.5%: consider

combination therapy

Yes, metformin + insulin

If A1C ≥9%: consider insulin

Yes, Basal insulin started, titrated

against FPG

Start once-a-day long-acting insulin analog or NPH bedtime or morning

Starting dose 10 units or 0.2 units/kg

Titrate against FPG until in target range (70–130 mg/dL) Increase dose typically by 2 units q 3 days

Can increase dose by 4 units q 3 days if BG >180 mg/dL

Initiation and Adjustment of Insulin Regimens

Adapted from Nathan DM et al. Diabetes Care. 2009;32(1):193–203.

If hypoglycemia occurs or if BG <70 mg/dL

Reduce dose by ≥4 U, or by 10% if dose is >60 U

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Philip Sees Primary Care Physician at 6 Months

• Basal insulin dose is 30 units, FPG is between 80 and 110 mg/dL most days

• PPG is between 180 and 220 mg/dL

• BMI = 30 kg/m2

• He denies any symptoms of hypoglycemia

• How would you modify his injectable therapy?

– Continue to titrate basal insulin therapy?

– Add prandial insulin?

– Add a GLP-1 RA?

25

PPG = postprandial glucose.

26

Guideline Approach to Therapy in Patients With Newly Diagnosed Type 2 Diabetes

27

Raz I. Diabetes Care. 2013;36(suppl 2):S139–S144.

Step Action in Philip

Set A1C goal 7%

Lifestyle intervention ± metformin Metformin 1 mg bid Set up with dietitian, exercise trainer

If A1C ≥7.5%: consider combination therapy Yes, metformin + basal insulin

If A1C ≥9%: consider insulin Basal insulin started, titrated against FPG (conservative dosing – discontinuation of nutritional and correction dosing used in hospital) With SMBG 1–4 times/day orders for test strips, lancets, syringes, needles (unless a pen ordered), and a glucagon kit

If A1C not at target (3–6 months), add an agent, depending on BMI

BMI <30 kg/m2 35> BMI >30 kg/m2 BMI >35 kg/m2

DPP-4 inhibitor (Consider GLP-1 RA, SGLT-2 inhibitor)

GLP-1 RA, SGLT-2 inhibitors DPP-4 inhibitors

GLP-1 RA, SGLT-2 inhibitors Consider bariatric surgery in nonresponders

Role of Incretin-based Therapies in Reducing Hyperglycemia

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Ussher JR, Drucker DJ. Endocr Rev. 2012;33(2):187–215.

GLP-1 Receptor Agonists’ Place in Therapy: ADA/EASD Recommendations

• Second-line in addition to metformin

• In 3-drug combinations

• With basal insulin

• Among preferred agents in specific situations

– When goal is to avoid hypoglycemia

– When goal is to avoid weight gain

• Actions complement those of commonly used antihyperglycemic agents

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Class Effectiveness Cellular Mechanism Primary Physiologic Actions

Insulin Highest Activate insulin

receptors

↑ Glucose disposal

↓ Hepatic glucose production

GLP-1 RA High Activate GLP-1

receptors

↑ Insulin secretion (glucose dependent)

↓ Glucagon secretion (glucose dependent)

↑ Satiety

Inzucchi SE et al. Diabetes Care. 2012;35(6):1364–1379.

GLP-1 Receptor Agonists’ Place in Therapy in the AACE 2013 Algorithm

• Recommended for treatment-naïve patients at every A1C level as

– Monotherapy or

– Part of combination-therapy regimens

• Both oral or with insulin

• Based on multifactorial mechanism of action, glucose-dependent mechanism of action (low risk of hypoglycemia), and potential for weigh loss/no risk of weight gain

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Garber AJ et al. Endocr Pract. 2013;19(3):536–557.

Marketed GLP-1 Receptor Agonists

Characteristic Exenatide bid Liraglutide Exenatide ER Albiglutide Dulaglutide

Initial US approval

2005 2010 2012 2014 2014

Trade name Byetta® Victoza® Bydureon® Tanzeum® Trulicity®

Description

Synthetic exendin-4, a peptide identified in H. suspectum; activates GLP-1 receptors and is resistant to DPP-4 degradation

GLP-1 modified to be resistant to DPP-4 degradation

Exenatide contained in hydrolyzable polymer microspheres for extended release

GLP-1 modified to be resistant to DPP-4 degradation

GLP-1 modified to be resistant to DPP-4 degradation

Administration Subcutaneous injection

Half-life 2.4 hours 13 hours >1 week 5 days 5 days

Dosing 2× daily,

before meals 1× daily, anytime

1× weekly 1 × weekly 1 × weekly

1. Byetta (exenatide) [prescribing information]. 2. Victoza (liraglutide) [prescribing information]. 3. Bydureon (exenatide extended-release for injectable suspension) [prescribing information]. 4. Tanzeum (albiglutide) [prescribing information]. 5. Trulicity (dulaglutide) [prescribing information].

GLP-1 Receptor Agonists

32

FDA-Approved Agents • Liraglutide

• Albiglutide

• Dulaglutide

• Exenatide

• Exenatide ER

Key Features • Injectable administration

• Mimic action of native GLP-1

• Increase glucose-dependent insulin secretion

• Suppress glucagon production in glucose-dependent manner

• Slow gastric emptying

• Increase satiety (reducing appetite/food intake)

ER = extended release; GLP-1 = glucagon-like peptide 1.

Garber AJ et al. Endocr Pract. 2013;19(suppl 2):1–48.

Monotherapy Add-on to Metformin Add-on to SU

Alb1 Dul2 Exe3 Exe

ER4

Lir5 Alb6 Dul7 Exe8 Exe

ER9

Lir10 Alb11,* Exe12 Exe

ER13,†

Lir14

Baseline A1C (%) 8.1 7.6 7.8 8.5 8.3 8.1 8.1 8.2 8.6 8.4 8.2 8.6 8.3 8.5

Glucose Control With GLP-1 Receptor Agonists

33

Placebo-adjusted Change From Baseline (Not Head-to-Head Trials)

*Metformin with or without SU or TZD. †Metformin with or without SU. ‡Absolute change from baseline (active-controlled trial).

1. Tanzeum (albiglutide) injection [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2014. 2. Umpierrez G et al. Diabetes Care. 2014;37:2168–2176. 3. Moretto TJ et al. Clin Ther. 2008;30:1448–1460. 4. Russell-Jones D et al. Diabetes Care. 2012;35:252–258. 5. Garber A et al. Lancet. 2009;373:473–481. 6. Ahrén B et al. Diabetes Care. 2014;37:2141–2148. 7. Dungan KM et al. Lancet. 2014;384:1349–1357. 8. DeFronzo RA et al. Diabetes Care. 2005;28:1092–1100. 9. Bergenstal RM et al. Lancet. 2010;376:431–439. 10. Pratley RE et al. Lancet. 2010;375:1447–1456. 11. Pratley RE et al. Lancet Diabetes Endocrinol. 2014;2:289–297. 12. Buse JB et al. Diabetes Care. 2004;27:2628-2635. 13. Diamant M et al. Lancet. 2010;375:2234–2243. 14. Marre M et al. Diabet Med. 2009;26:268–278.

Pla

ceb

o-a

dju

sted

A1

C (

%)

‡

‡

‡ ‡

‡

‡

‡

‡

-1.0 -0.9

-0.8 -0.8

-1.4

-1.0

-0.7 -0.9

-1.5 -1.5 -1.5 -1.4

-1.1

-1.5

-2

-1.5

-1

-0.5

0

Monotherapy Add-on to Metformin Add-on to SU

Alb1 Dul2 Exe3 Exe

ER4

Lir5 Alb6 Dul7 Exe8 Exe

ER9

Lir10 Alb11,* Exe12 Exe

ER13,†

Lir14

Weight Change With GLP-1 Receptor Agonists

34

*Metformin with or without SU or TZD. †Metformin with or without SU.

1. Tanzeum (albiglutide) injection [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2014. 2. Umpierrez G et al. Diabetes Care. 2014;37:2168–2176. 3. Moretto TJ et al. Clin Ther. 2008;30:1448–1460. 4. Russell-Jones D et al. Diabetes Care. 2012;35:252–258. 5. Garber A et al. Lancet. 2009;373:473–481. 6. Ahrén B et al. Diabetes Care. 2014;37:2141–2148. 7. Dungan KM et al. Lancet. 2014;384:1349–1357. 8. DeFronzo RA et al. Diabetes Care. 2005;28:1092–1100. 9. Bergenstal RM et al. Lancet. 2010;376:431–439. 10. Pratley RE et al. Lancet. 2010;375:1447–1456. 11. Pratley RE et al. Lancet Diabetes Endocrinol. 2014;2:289–297. 12. Buse JB et al. Diabetes Care. 2004;27:2628–2635. 13. Diamant M et al. Lancet. 2010;375:2234–2243. 14. Marre M et al. Diabet Med. 2009;26:268–278.

W

eig

ht

(kg)

Absolute Change From Baseline (Not Head-to-Head Trials)

-0.9 -1.2

-0.6

-2.3 -2.6

-1.6

-3.1 -2.8

-2.6

-2 -2.3

-0.2

-2.5

-3.4 -4

-3

-2

-1

0

Monotherapy Add-on to Metformin Add-on to SU

Alb1 Dul2 Exe3 Exe

ER4

Lir5 Alb6 Dul7 Exe8 Exe

ER9

Lir10 Alb11,* Exe12 Exe

ER13,†

Lir14

Hypoglycemia With GLP-1 Receptor Agonists

35

*Metformin with or without SU or TZD. †Metformin with or without SU.

1. Nauck M et al. Diabetes. 2013;62(suppl 2): Abstr. 55-LB. 2. Umpierrez G et al. Diabetes Care. 2014;37:2168–2176. 3. Moretto TJ et al. Clin Ther. 2008;30:1448–1460. 4. Russell-Jones D et al. Diabetes Care. 2012;35:252–258. 5. Garber A et al. Lancet. 2009;373:473–481. 6. Ahrén B et al. Diabetes Care. 2014;37:2141–2148. 7. Dungan KM et al. Lancet. 2014;384:1349–1357. 8. DeFronzo RA et al. Diabetes Care. 2005;28:1092–1100. 9. Bergenstal RM et al. Lancet. 2010;376:431–439. 10. Pratley RE et al. Lancet. 2010;375:1447–1456. 11. Pratley RE et al. Lancet Diabetes Endocrinol. 2014;2:289–297. 12. Buse JB et al. Diabetes Care. 2004;27:2628–2635. 13. Diamant M et al. Lancet. 2010;375:2234–2243. 14. Marre M et al. Diabet Med. 2009;26:268–278.

Percentage of Patients Reporting Hypoglycemia (Not Head-to-Head Trials)

Pat

ien

ts (

%)

0 3

10.4 12.3

9

36

4.0 5.0

13.0

5.2 1

8.1 8

3

0

5

10

15

20

25

30

35

40

GLP-1 Receptor Agonist Weight Effects in Patients With T2DM

36

Meta-analysis of Published Studies

*Weight changes in patients treated for ≥12 weeks .

Aroda VR et al. Clin Ther. 2012;34:1247–1258; Buse JB et al. Lancet. 2009;374:39–47; Drucker DJ et al. Lancet. 2008;372:1240–1250; Blevins T et al. J Clin Endocrinol Metab. 2011;96:1301–1310; Rosenstock J et al. Presented at: 47th EASD Annual Meeting. 2011; Abstract 786; Buse J et al. Lancet. 2013;381:117–124; Pratley RE et al. Presented at: 72nd ADA Scientific Sessions. 2012; Abstract 945-P.

∆ W

eig

ht*

(kg

)

Exenatide Exenatide ER Liraglutide

-2.03

-2.29 -2.41

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

75% of patients lost weight With exenatide bid or exenatide ER: • ~10% lost >10 kg • ~20% lost 5–10 kg • ~48% lost 0–5 kg • ~20%–23% gained 0–5 kg • ~1%–2% gained 5–10 kg

Safety Considerations With GLP-1 Receptor Agonists

GI adverse events

• Common • Usually dose-dependent and transient • Usually reduced with dose titration

Pancreatitis

• Pancreatitis has been reported with postmarketing use of some of incretin agents, although no causal relationship has been established

• Extensive review by FDA of studies involving >80,000 patients has not uncovered reliable evidence of increased pancreatic risk with incretins vs. other agents

• Labeling for all incretins states these agents should be immediately discontinued if pancreatitis is suspected

• Labeling for GLP-1 receptor agonists suggests consideration of other therapies for patients with a history of pancreatitis

Renal impairment

• Renal Impairment has been reported postmarketing, usually in association with nausea, vomiting, diarrhea, or dehydration. Use caution when initiating or escalating doses in patients with renal impairment. Exenatide is contraindicated in patients with severe renal insufficiency or ESRD

CV • Small increase in pulse rate with these agents, although the clinical significance is not known

37

ER = extended release; MTC = medullary thyroid carcinoma.

Garber AJ et al. Endocr Pract. 2013;19(suppl 2):1–48. ADA/EASD/IDF statement concerning the use of incretin therapy and pancreatic disease [news release]. Alexandria, VA: American Diabetes Association, European Association for the Study of Diabetes, International Diabetes Federation; June 28, 2013. http://www.diabetes.org/newsroom/press-releases/2013/recommendations-for.html.

Safety Considerations With GLP-1 Receptor Agonists

Pancreatic cancer

• Extensive review by FDA of studies involving >80,000 patients has not uncovered reliable evidence of increased pancreatic risk with incretins vs. other agents

• Further assessments required from long-duration controlled studies or epidemiologic databases

Medullary thyroid cancer

• Animal data showed an increased incidence of C-cell tumors with liraglutide and exenatide ER treatment, but confirmatory population studies are lacking

• Labeling for albiglutide, dulaglutide, exenatide ER, and liraglutide: • Patients should be counseled regarding MTC and the signs/symptoms of thyroid

tumors • Contraindicated in patients with personal/family history of MTC or multiple

endocrine neoplasia syndrome type 2

38

ER = extended release; MTC = medullary thyroid carcinoma.

Garber AJ et al. Endocr Pract. 2013;19(suppl 2):1–48. ADA/EASD/IDF statement concerning the use of incretin therapy and pancreatic disease [news release]. Alexandria, VA: American Diabetes Association, European Association for the Study of Diabetes, International Diabetes Federation; June 28, 2013. http://www.diabetes.org/newsroom/press-releases/2013/recommendations-for.html.